The objectives of this investigation are to assess the distribution and effects in mammalian tissue of a group of naturally occurring tetrahydroisoquinolines (TIQs) which are derived from alpha-keto acids and catecholamines. Utilizing computerized gas chromatography-mass spectrometry emphasis will be placed on the regional localization of the norlaudanosolinecarboxylic acids (NLCAs) in human and rat brain of subjects maintained on normal L-3,4-dihydroxyphenylalanine (L-dopa) plus or minus carbidopa supplemented diets. 3'-0-methylNLCA (MNCLA) will be isolated from rat brain in amounts to permit a complete structure elucidation including assignment of the configuration of C-1 if a single enantiomeric form is obtained. Neuropharmacological studies will include experiments designed to detect stereotypy upon intracranial administration of NLCAs and their metabolites to determine their ability to bind to opiate receptors, and to evaluate their action on neuroendocrine control of lutenizing hormone, follicle stimulating hormone and prolactin. Effects of NLCAs on enzymes of catecholamine metabolism both in vitro and in vivo will continue using for the latter studies, cultured adrenal medulla explants and rats intracranially administered NLCAs. The mechanism of the inhibition of dopamine-beta-hydroxylase by MNLCA will be delineated. The biotransformation of NLCAs in mammalian brain will be examined and their possible conversion to morphinandienone derivatives evaluated by radioimmunoassay. The action of 3',4'-desoxyNLCA (DNLCA) and its metabolites on the myelineation process in developing mouse brain will also be determined. Since NLCAs have been found to accumulate during L-dopa chemotherapy of Parkinsonism and in a model phenylketonuria in those regions of brain in which pathological manifestations are observed, their role in these processes will be evaluated by this investigation.